Probes for the diagnosis of infections caused by Streptococcus pyogenes

ABSTRACT

The DNA from the bacteria  Streptococcus pyogenes  is extracted, then completely digested with restriction enzyme HindIII, followed by cloning into a suitable vector to select a probe comprising DNA which is essentially contained in  Streptococcus pyogenes , then the sequence of the probe is elucidated.

FIELD OF THE INVENTION

The present invention relates to a probe which is useful for detectingand identifying Streptococcus pyogenes, the causative bacteria ofinfectious diseases such as pharyngitis, rheumatic fever, nephritis,erysipelas, scarlatina, sepsis and the like.

BACK GROUND ART

Generally, the diseases caused by infection of pathogenic microorganismsare called infectious diseases. In pathology, “infection” is defined asan invasion of pathogenic microorganisms (hereinafter referred to as“bacteria”) and an establishment of footholds for the growth in the hostorganism by the pathogenic microorganisms. Thereafter, the outbreak ofthe disease states caused by proliferation of the pathogenicmicroorganisms in vivo depends upon the relationship between theresistance of the host and the virulence of the bacteria.

Streptococcus is a genus of gram-positive facultative or obligateanaerobe, which exhibits the chain like arrangement. According to thecharacteristic appearances of hemolytic rings formed around the coloniesgrown on blood agar medium, the member of this genus is classified intothree types: α, β, and γ. Moreover, the members of this genus arefurther classified into 20 groups from A to V (except I and J) independence upon their antigenicity of C-polysaccharide contained in thebacteria (Lancefield classification).

Streptococcus pyogenes is a member of Streptococcus Group A underLancefield classification, which shows β-type hemolysis (i.e., completehemolysis), and is of clinical importance as causative bacteria of humanpharyngitis, tonsillitis, scarlatina, erysipelas, puerperal fever,sepsis and the like. It is also known as the causative bacteria for theallergic diseases which are referred to as post-streptococcal diseasessuch as rheumatic fever or nephritis secondary to the initial infection.Furthermore, in recent years, the cases that exhibit severe septic shockwith myositis (fulminant type Streptococcus Group A infection) due toStreptococcus pyogenes infection have been also reported.

The patient suffering from pharyngitis upon Streptococcus pyogenesinfection generally complains sore throat with significant erythrogenicpharynx and trachelopanus as well as pharyngeal pain, therefore, theseclinical symptoms may suggest the infection of the bacteria and lead tothe possible diagnosis. However, it is desirable to avoid theunnecessary administration of antibacterial agents while the optimalchemical therapy is extremely important to prevent the complicationssecondary to the infection, and in view of some cases not accompanied byevident clinical symptoms, development of the rapid and accuratebacteriological diagnosis has been desired.

In addition, in the case of fulminant type Streptococcus Group Ainfection, more than 50% of the cases were reported to result incomplications with severe necrotizing tasciitis, therefore it can beeasily progressed to multiple organ failure and even to death.

Streptococcus pyogenes is generally known to be highly sensitive toβ-lactam agents such as ampicillin and cefaclor. However, approximately30% of the bacterial strains are highly resistant to erythromycin, andthe appearance of ofloxacin resistant strains has also been reported,therefore, the most attention has to be paid at administration withmacrolide derivatives or new-quinolone derivatives.

Consequently, it is essentially important to perform the accuratediagnosis at an early stage of infection and select the optimalantibacterial agents in the cases of the infectious diseases caused byStreptococcus pyogenes as described above.

In general biological procedure, it is mandatory to: (1) analyze theclinical symptoms; (2) culture the specimen; and (3) isolate andidentify Streptococcus pyogenes from the cultures, and then thetherapeutic strategy is determined after these items are sufficientlyexamined.

The method to identify Streptococcus pyogenes comprises direct smearculturing of the specimen on a blood agar plate which is supplementedwith 5% sheep or horse defibrinated blood and monitoring thecharacteristic appearances of the hemolytic rings around the coloniesgrown on the plate.

However, it is always accompanied by the difficulties in theidentification of the causative bacteria. Actual identification of thecausative bacteria is quite difficult because of a variety of shapes ofthe colonies which are formed dependent upon the culture conditions,thus, the identification is avoided. Also, the bacteria from thespecimen have to be proliferated for a long time in the appropriatemedium to the number large enough for applying the drug sensitivitytest, and then at least 3 to 4 days of incubation period is required toattain the result of the test. Thus the rapid diagnosis can not beachieved in accordance with the above process. Additionally, in cases ofthe diagnosis of the patients who had already been treated with a largedose of antibiotics when the possible infection was suspected, thegrowth and proliferation of the bacteria may be prevented even if thebacteria are present in the specimen. Accordingly, the feasibility ofsuccessful culture of the bacteria from these specimen may becomeextremely low.

Furthermore, alternative subroutine methods developed heretofore mayinclude: an instrumental analysis method of constituents of bacteria andmetabolic products from bacteria (See Yoshimi Benno, “Quickidentification of bacteria with gas chromatography”, Rinsho Kensa, Vol.29, No.12 pp.1618-1623, November 1985, Igaku Shoin.); a method utilizinga specific antibody (See Japanese Patent Provisional PublicationNo.60-224068.); and a hybridization method utilizing a specificity ofDNA (Japanese Patent Provisional Publication No. 61-502376), however,any of which requires the steps for isolation of the bacteria, as wellas the steps for culturing and growing the bacteria.

On the other hand, an established method based on the function of thephagocyte in the infectious diseases has been proposed, wherein astained smear of buffy coat in which leukocytes constituents in theblood sample are concentrated is examined under an optical microscope.Generally speaking, the detection rate of bacteria in buffy coatspecimens from adult bacteremia patients is 30% at most, which issimilar to that in blood specimens from ear lobes, however, it wasreported that in case that the patients are newborn children, thebacteria could be detected in seven cases in ten (70%). Therefore,information concerning the presence of bacteria in peripheral bloodobtained by a microscopic prospection on a smear can provide animportant guiding principle for the therapeutic treatment.

The above mentioned conventional methods necessitate the pretreatmentwhich requires at least three to four days in total, containing one totwo days for the selective isolation of bacteria from a specimen, oneday for proliferating cultivation, and one or more days for operation offixation, and the culture thereof should be continued in practice untilthe bacteria grow enough, therefore, the pretreatment may require oneweek or more days. In addition, any bacteria other than the causativebacteria may be contaminated during the culture step in some cases, andsuch contaminants may not be distinguished from the causative bacteria.

More importantly, as mentioned above, because many of the causativebacteria in the specimen to be proliferated and detected have beenuptaked into phagocytes, and are already dead or in a bacteriostaticstate due to the antibiotics administered, the number of bacteria thatcan be grown may be small even under appropriate conditions for theculture of the causative bacteria, thereby, the actual detection rate ofbacteria is as low as about 10% when the clinical culture specimen isemployed. In the other words, for the present, 90% of the examined bloodfrom the patient clinically suspected as suffering from the infection ofStreptococcus pyogenes could not be identified for the presence of thebacteria after all, even though the culture is continued for further oneor more days.

Although the determination of the causative bacteria and selection ofthe antibiotics suitable for killing the bacteria as quick as possiblehave been eminently desired, in light of the present situation as above,the presently employed practice depends upon a therapeutic treatmentwhich is initiated when the infection of Streptococcus pyogenes isclinically suspected without awaiting the results of the detection ofthe causative bacteria. That; is to say, a trial and error method hasbeen practiced wherein an antibiotic having the effectiveness for thewidest range of spectra against many kinds of bacteria is administeredfirst, and next, if the antibiotic is shown to be not effective afterone or two days, another antibiotic will be tested.

Recently, rapid methods for the diagnosis of-the infections ofStreptococcus pyogenes to immunologically detect the bacteria using theprocedures such as latex agglutination assay, co-agglutination assay,enzyme immunoassay, gold particle assay and liposome immunoassay havebeen developed. All of these methods are carried out by extractingC-polysaccharide on the surfaces of the bacterial bodies ofStreptococcus pyogenes with nitrous acid or enzymes, and detecting thepresence of the bacteria using the polysaccharide as an antigen.

However, the above immunological methods are problematic because theresults thereof are often inconsistent with the results obtained by theculture method (namely, indicating false positive or false negativeresults), and because the manipulation for carrying out the methods arecomplicated.

Further, species specificity of this immunological method is notsatisfactory due to the properties of this diagnosis method in whichantigen-antibody reactions are utilized, namely, detection of thebacteria except for Streptococcus pyogenes, which carry Group A antigen(e.g., Streptococcus anginosus, and the like) may be obliged.

Meanwhile, a diagnostic guideline for the clinical diagnosis of theinfections caused by fulminant Group A Streptococcus has been alsoproposed JAMA, Vol.269, 390-391, 1993), however, it is not applicable tothe early diagnosis.

Although the infectious diseases caused by Streptococcus pyogenes arediseases of which rapid and accurate diagnosis has been required, theconventional diagnosis method could not have complied with such demands.

DISCLOSURE OF THE INVENTION

The present invention was accomplished in view of the above-describedproblems in this art, and is directed to probes which have the specificreactivities toward DNA or RNA derived from causative bacteria ofinfectious diseases, specifically Streptococcus pyogenes, and toelucidation of the nucleotide sequences of the portions of the geneessentially derived from Streptococcus pyogenes, which should becomprised in the probe.

Accordingly, the bacterial DNA still included in the bacteria but in theprocess of breakdown through phagocytosis by phagocytes can besignificantly detected based on its specificity using hybridizationmethod. Therefore, rapid and accurate detection of the causativebacteria of infectious diseases can be achieved without culturing andproliferation of the bacteria. Moreover, identification of the causativebacteria can be accomplished through DNA amplification using PCR methodwithout the hybridization process when a primer is designed withreference to the nucleotide sequence information of the probes of thepresent invention.

In addition, the probe used for the hybridization may be labeled withnon-radioactive agent. If biotinylated probe is used for example, thedetection can be carried out in a general examination laboratory nothaving a facility for radioisotope handling. Thus, operation for thedetection can be practiced in a rapid and simple way.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1(a) is a drawing which shows the positions of the originatedbacterial strains of the DNAs on each of the filters of dot blothybridization, and

FIG. 1(b) shows the results obtained by color development after thehybridization process using each probe.

BEST MODE FOR CARRYING OUT THE INVENTION

In order to explain the present invention in more detail, non-limitingExamples with respect to the probes which are derived from Streptococcuspyogenes, causative bacteria of infectious diseases are shown below.

EXAMPLE 1 DNA Probe Derived from Streptococcus pyogenes

(1) Preparation of DNA probes derived from the bacteria Streptococcuspyogenes

Clinical isolate of Streptococcus pyogenes was cultured overnight in BHI(Brain Heart Infusion) medium, then the cultured cells were harvested,and genomic DNA was extracted therefrom in accordance with Saito-Miuramodified method (“Preparation of transforming deoxyribonucleic acid byphenol treatment”, Biochem. Biophys. Acta vol. 72, pp.619-629 (1963)) inwhich cell lysis step was carried out by adding N-Acetylmuramidase SG tothe lysis buffer.

The extracted DNA was completely digested with restriction enzymeHindIII, then random cloned into vector pGEM-3Z. Six probes specific toStreptococcus pyogenes, that is to say, the probes comprising DNAfragments which showed specific reactivities toward DNA included innatural Streptococcus pyogenes, were selected from thus obtained clones.

Thereafter, the selected probes were named: probe SP-6-28, probeSP-7-44, probe SP-14-1, probe SP-26-36, probe SP-26-46, and probeSP-55-3.

(2) Studies of species specificity of the DNA probes derived fromStreptococcus pyogenes

Interactions between each probes and DNAs from several kinds ofcausative bacterial strains of infections were studied as follows.

First, the clinical isolates and deposited bacterial strains as listedin Table 1 below were prepared. In order to obtain the sources of Humangenomic DNA in Table 1 and a control sample, leucocytes which werecollected from four healthy adult men, and Escherichia coli K-12, JM109transformant containing plasmid pGEM-3Z were respectively prepared.

TABLE 1 Bacteria No. Abbrev. Name Origin 1 SP Streptococcus pyogenesClinical Isolate 2 SAG Streptococcus agalactiae Clinical Isolate 3 SPNStreptococcus pneumoniae NYSDH DP-2 4 SA Staphylococcus aureus ATCC25923 5 SE Streptococcus epidermidis ATCC 12228 6 EC Escherichia coliATCC 25922 7 KP Klebsiella pneumoniae Clinical isolate 8 EBCEnterobacter cloacae Clinical Isolate 9 EF Enterococcus faecalisClinical Isolate 10 PA Pseudomonas aeruginosa ATCC 27583 11 HINHaemophills influenzae Clinical Isolate 12 HUM U937 Human Genomic DNA

Abbreviation

NYSDH: New York State Department of Health (Albany, N.Y., U.S.A.)

Thereafter, the DNAs included in each of the clinical isolates wereextracted according to the method described in Example 1(1), then thealiquot of the extracted DNA (e.g., 10-100 ng) was spotted onto a nylonfilter. After denaturation with alkali, the filter was subjected to dotblot hybridization. The human genomic DNA sample was prepared from theleukocyte obtained as mentioned previously using Saito-Miura modifiedmethod (supra). A control sample was prepared from Escherichia coliK-12, JM109 transformant containing plasmid pGEM-3Z using the method forpreparation of plasmid DNA described in the following Example 2(1).Hybridization was then carried out overnight using a Digoxigenin-11-dUTP(BRL) labeled DNA probe which was derived from the Streptococcuspyogenes under a hybridization condition of 45% formamide, 5×SSC, at 42°C. according to Manual by Maniatis (T. Maniatis,et al., “MolecularCloning (A Laboratory Manual Second Edition)”., Cold Spring HarbourLaboratory (1989)).

After overnight hybridization was completed, the samples were washed twotimes with 0.1×SSC, 0.1% SDS at 55° C. for 20 min. according to themanual, followed by color development and detection using Anti-Dig-ALPconjugates (BRL), thus results of hybridization were revealed. Theseresults are shown in FIG. 1, wherein FIG. 1(a) illustrates the positionsof the originated bacterial strains of the DNAs on each of the filtersof dot blot hybridization, and FIG. 1(b) illustrates the resultsobtained by color development after the hybridization process using eachof the above mentioned probes SP-6-28, SP-7-44, SP-14-1, SP-26-36,SP-26-46 and SP-55-3.

The experimental results with respect to the reactivities between eachprobes and DNAs from each of the clinical bacteria strains are shown inTable 2 below.

TABLE 2 Bacteria Probe (Denotation: SP-) No. Abbrev. Name 6-28 7-44 14-126-36 26-46 55-3 1 SP Streptococcus pyogenes + + + + + + 2 SAGStreptococcus agalactiae − − − − − − 3 SPN Streptococcus pneumoniae − −− − − − 4 SA Staphylococcus aureus − − − − − − 5 SE Staphylococcusepidermidis − − − − − − 6 EC Escherichia coli − − − − − − 7 KPKlebsiella pneumoniae − − − − − − 8 EBC Enterobacter cloacae − − − − − −9 EF Enterococcus faecalis − − − − − − 10 PA Pseudomonas aeruginosa − −− − − − 11 HIN Haemophills influenzae − − − − − − 12 HUM U937 HumanGenomic DNA − − − − − −

Remarks

+: hybridization signal detected

−: hybridization signal not detected

As is evident from the Tables 1 and 2 above, all of the present probesshowed reactivities only to the DNA derived from Streptococcus pyogenes,while no reactivity (i.e., hybrid formation) was observed toward theDNAs from the every other bacterial species in the genus Streptococcus,as well as the DNAs from the bacterial species other than genusStreptococcus. Thus, the specificity of the probes was demonstrated.

EXAMPLE 2 Analysis of the Base Sequence

Each of the base sequences of the DNA probes (six probes in total) ofwhich species specificity was demonstrated in Example 1 as above wasdetermined according to the following procedure.

(1) Preparation of Plasmid DNA

Escherichia coli K-12, JM109 transformant, wherein the sub-cloned insertfragment (to be sequenced) is contained in pGEM-3Z (Promega), wasinoculated into 5 ml of Luria-Bactani Medium (bacto-tryptone, 10 g/1 L;bacto-yeast extract, 5 g/1 L; NaCl, 10 g/1 L; adjusted pH to 7.0 with 5NNaOH) and cultured overnight.

The culture liquid mixture was centrifuged (5,000 rpm, 5 min.) tocollect the bacteria. One hundred μl of a solution of 50 mM glucose/50mM Tris-HCl (pH8.0)/10 mM EDTA containing 2.5 mg/ml of lysozyme (Sigma)was added to the precipitate, and left at room temperature for 5minutes. To the suspension, 0.2M NaOH solution containing 1% of sodiumdodecyl sulfate (Sigma) was added and mixed. One hundred and fifty μl of5M potassium acetate aqueous solution (pH 4.8) was further added theretoand mixed, then cooled on ice for 15 minutes.

The supernatant collected by centrifugation (15,000 rpm, 15 min.) of themixture was treated with phenol/CHCl₃, and ethanol of two times byvolume was added thereto, then the precipitate was again obtained bycentrifugation (12,000 rpm, 5 min.). This precipitate was dissolved in100 μl of a solution of 10 mM Tris-HCl (pH7.5)/0.1 mM EDTA, followed byaddition of 10 mg/ml RNase A (Sigma) solution, then the mixture was leftat room temperature for 15 minutes.

Three hundred μl of 0.1M sodium acetate aqueous solution (pH 4.8) wasadded to this mixture and treated with phenol/CHCl₃, then theprecipitate was obtained therefrom by adding ethanol to the supernatant.This precipitate was dried and dissolved in 10 μl of distilled water togive a DNA sample.

(2) Pretreatment for Sequencing

Pretreatment for sequencing was performed with AutoRead™ Sequencing Kit(Pharmacia).

Concentration of DNA to be employed as a template was adjusted to 5-10μg in 32 μl of a solution. Thirty two μl of the template DNA solutionwas transferred to a mini-tube (1.5 ml, Eppendolf), and added thereto 8μl of 2M NaOH aqueous solution, then mixed gently. After instantcentrifugation, it was left at room temperature for 10 minutes.

Seven μl of 3M sodium acetate (pH 4.8) and 4 μl of distilled water wereadded, followed by 120 μl of ethanol, and after mixing, the mixture wasleft for 15 minutes on ethanol/dry ice. DNA which was precipitated bycentrifugation for 15 minutes was collected, and the supernatant wasremoved carefully. The precipitate thus obtained was washed with 70%ethanol and centrifuged for 10 minutes. Then, after the supernatant wascarefully removed again, the precipitate was dried under the reducedpressure.

The precipitate was dissolved in 10 μl of distilled water, then 2 μl offluorescent primer (0.42 A₂₆₀ unit/ml, 4-6 pmol [Fluorescent Primer;Universal Primer: 5′-Fluorescein-d[CGACGTTGTAAAACGACGGCCAGT (SEQ ID NO:7)]-3′ (1.6 pmol/μl, 0.42 A₂₆₀ unit/ml); Reverse Primer:5′-Fluorescein-d[CAGGAAACAGCTATGAC (SEQ ID NO: 8)]-3′ (2.1 pmol/μl, 0.42A₂₆₀ unit/ml), and 2 μl of annealing buffer was added thereto, and mixedgently.

After instant centrifugation, the mixture was heat-treated at 65° C. for5 minutes and rapidly transferred to a circumstance of 37° C. and keptthe temperature for 10 minutes. After keeping the temperature, it wasleft at room temperature for more than 10 minutes, and centrifugedinstantly.

Then, the sample was prepared by adding thereto 1 μl of elongationbuffer and 3 μl of dimethyl sulfoxide.

Four mini-tubes have been identified with one of the marks of “A”, “C”,“G” and “T”, and, according to the respective mark, 2.5 μl of A Mix(dissolved ddATP with dATP, dCTP, c⁷dGTP and dTTP), C Mix (dissolvedddCTP with dATP, dCTP, c⁷dGTP and dTTP), G Mix (dissolved ddGTP withdATP, dCTP, c⁷dGTP and dTTP), or T Mix (dissolved ddTTP with dATP, dCTP,c⁷dGTP and dTTP) was poured into each identified tube. Each solution waspreserved on ice until use, and was incubated at 37° C. for one minuteor more before use.

Two μl of diluted T7 DNA polymerase (Pharmacia; 6-8 units/2 μl) wasadded to the DNA sample, and completely mixed by pipetting or mixing itgently.

Immediately after completion of the mixing, the mixed solution wasdistributed to 4.5,μl of the four types of the solutions respectivelywhich had been incubated at the same temperature. Fresh tips were usedfor each distribution.

The solutions were kept for 5 minutes at 37° C., then 5 μl oftermination solution was added to each reaction mixture.

Fresh tips were also used for this step. Immediately after incubatingthe solution for 2-3 minutes at 90° C., it was cooled on ice. Four tosix μl of the solution per lane was applied for the electrophoresis.

(3) Sequencing on Base Sequences

Sequencing on the base sequences of the probes disclosed in Examples 1and 2, having the specificity toward DNA from Streptococcus pyogenes wasperformed using A.L.F. DNA Sequencer System (Pharmacia) under acondition of the electrophoresis process of 45° C. for 6 hours. Primerswere serially designed based on the sequences elucidated from each ofthe upstream and downstream sequences, and the above describedprocedures were repeated.

Consequently, all of the entire base sequences of the probe SP-6-28 (SEQID NO: 1), probe SP-7-44 (SEQ ID NO: 2), probe SP-14-1 (SEQ ID NO: 3),probe SP-26-36 (SEQ ID NO: 4), probe SP-26-46 (SEQ ID NO: 5) and probeSP-55-3 (SEQ ID NO: 6) were elucidated.

INDUSTRIAL APPLICABILITY

Using the probes according to the present invention, the causativebacteria which were incorporated into the phagocytes can be rapidly andaccurately identified directly without proliferation of the bacteria byfor example, a hybridization method. In other words, the diagnosiswherein the probes of the present invention are used enables theidentification of the causative bacteria with single specimen, further,the necessary time for diagnosis can be diminished to approximately 1 to2 days, while the conventional method with low detection rate requires3-4 days, and the resulting detection rate is remarkably improved.

Therefore, the present invention provides guiding principles of thetherapeutic treatment for the infectious diseases caused byStreptococcus pyogenes, in addition, the effective treatment in an earlystage of the infection can be adopted to the patients, which may lead toa reduction of the mortality.

Additionally, in accordance with the present invention wherein the basesequences of the probes which specifically react with the DNA derivedfrom Streptococcus pyogenes among other several causative bacteria ofthe infectious diseases were elucidated, artificial preparation of theseprobes has become feasible. Moreover, a part of the information of thebase sequences provided herein may be utilized to produce primers, whichare useful for rapid diagnosis through amplification of DNA of causativebacteria contained in the clinical specimen by a PCR method.

Furthermore, the rapid identification of the causative bacteria may becarried out by comparing the base sequences of the genomic DNA from theclinical specimen with the base sequences provided by the presentinvention.

As stated above, the present invention provides the desired probe forthe diagnosis of the infections, besides, outstanding utilities asguiding principles for the manufacture of the primers for PCR as well asstandard sequences which are suitable for the comparison of genomic DNAcontained in the clinical specimen can be expected. Moreover, thepresent invention may exert beneficial effects by providing valuableclues for preparation and development of the novel probes whichspecifically react with the DNA from the causative bacteria of theinfectious diseases.

Further, the base sequence disclosed in the present application wasobtained by random-cloning of the genomic DNA from the clinicalisolates, therefore, the utilities of the base sequences of the presentinvention should be encompassed to the complementary strand thereof.

Additionally, it may be presumed that DNA obtained from the wild strainsmight contain the mutated portion. However, as apparent from thedisclosure of the Examples above, such mutated DNA portion would notaffect the utilities which should be derived from the present invention,comprising the specificity of the probe of the present invention in thehybridization procedure for the diagnosis of the infections, and usagesof the information on the base sequences disclosed in the presentapplication for designing the primer to be employed for the PCRtechniques with the aim of a rapid diagnosis of the infections.

8 3549 base pairs nucleic acid double linear DNA (genomic) Streptococcuspyogenes Clinical Isolate SP-6-28 1 AAGCTTGTGC TGCTGCACCA CTAGCGTTTGAAAAATGAGT GTTAGTCATG CCTAATTGTT 60 TGGCTGTGGC ATTAATACGA TCGATAAACGCAGAAGCATC ATTGTTTGAT AAATAATTGG 120 CAATCATAAC AGTTGCTGCA TTTGATGAAGGCACAGCTGT CATAGTAATA AGATCACGAA 180 TAGGATAAGC TACTCCAGCG ACGATATTATTATTGCTAAT CTCATAAATG TTAGCGATAG 240 CTTGATCGGT TGGAGTTGCC GTAATAGTAGTGTCCATCGT AATTTTTCCC TTAGCGAGCT 300 CTTCAAATAA AATGTAAAGC GTAAACATTTTAGACATACT AGCAGGATCC CTAGGAATAT 360 CAATATTATC TTGCCAAAGA ATATCTGAACTATTTGCATC AACGACAATA GAAGATTTTG 420 GTCGATTAAC CTCACTAACT GTGTAGCCTGCTTGCCTTGT AATATCCATG ACATCTTCGG 480 CTTGGACAAG AGGCATCACC GAAAAGCAAATAAAGGTAAA AATAGTTAGT ATAATTCTTT 540 TGGTCAATTT CCGACTCCTT TAAATGTAATGCATTTTCAG TATATCACTT TGCTAATACA 600 ATGTGAAGTT TTTTTGAAAA ATTGTTAGGATTGGCCTAGT TTGCTTAAAT AAAAATGAAA 660 AAGACTGCAG AAGTACTCTG TCAGTCAATGTCATACAAAA AGCATTGTGT TATTCTATAA 720 AGAGGTATTG ACATACCTCA CAAAACGGTTCCACCAGACC TTTAAAAAGA AACTTTTAGA 780 AATGTTTTTT TGAAGGATAA GATTGATAGAAGGAGGAGTA TCCAGATAAC CCTGTCCAAT 840 AAGATGTTTA TCTTGAAGGG TTGCTCTACCTAAGACTTGT CCCTTTGATA GAGGTGCGAT 900 CATTGTGGAT GATTTCTTAG TAATATGGACGGTATTTTTG GTCTTTGTAT GTATTGGTTT 960 GATAAAAAAT AAACTATTTT GGGCTACAAGTTTGACAGTT TTTTCAGGAC TGTCTAAGAC 1020 AGATAACGTT TTTACTGGTT TATTATTTTCAATTAACTGG ACTTTTTGAA AATTAATTAA 1080 AAGGTACTGC AACAATTGAT TGGTTGTTTTAAATATAGCT AAATCATCCT CGTGGCTTTG 1140 ATCAGCATTT AAAACTACTG TAATAACCCTCATTTGATTT TCGACACTAG TAGCTACAAA 1200 AGAAGCACCG GCTTTTTTAG AATAACCAACAAAAAGACCA TCCACGCCTT CTCGATAACA 1260 AGGCATGCCT TTAAGCATGT AATTATAACTGTAAATGGTT TGTCCATCAA AAATAGTGGA 1320 GGATTTGCTA GATAATTTCA GTACTTCTGGAAATTCTAAT AAGAGATGCC TGGCAATAAT 1380 AGCTAAATCA GTGGCGCAAA AACAATTTTCGTCATCTGGT TCTGTATTAG GATAAGTATT 1440 AGCTCCTAAA AAATGGTTAG TTAAGCCAGTTGAATTAACG ACCTTTGCAT CGGAAATGCC 1500 CCATTGCCTT AATTGTTTTT TCATTTTGTCAACAAATTTG GGTTCGGTTC CGCCTATTTT 1560 TTCAGCTAAA GCAATAGCGG GGCTATTGGCGTTATTAACA ACTAACGCAC TTAAAAGTTC 1620 TTTAACGGTA TATTTTCTCT TATCAAGAGGAACGTTACTA ATAGTATAGT TTGTAGTGAG 1680 TTCATAAGGG TAGTTAGAAA TAGTTACAGGACTATCCCAA TTTAGCTTGC CCTTAGAAAC 1740 TTCTTTGTAA ACCAGATAGG TTGTCAAGAGCTTACTGACT GAGGCGACTG GGACAACCTT 1800 CTTTAGTATC TTTTTCGTAT AAAACTTTGCCACTTTCAAG GTCAACGGCA ATCGCATGCT 1860 TAGCAGTTAC CGAATACTCT TCACCGCTAACAGTGCTTGC TGCAAAAAAT AAGGCGATGA 1920 CCACTAGGGA AATTAATCGT TTGATCATTTATAGATTATC CTTACTCAAG TATTATTTTT 1980 TTAATTATAC CATATTTTTG TCTAAGGTAATGACTTACCT CACAAGAGTA GTGATGCAAT 2040 AAAACGCTAC CATGAGAGAA TGACAATCTTTATTAAACTA ATTGAAACCT CATTAAAAAA 2100 GGGGTATAAC GCTTTCATAT AGATAAATGTATAAAATAAA GAAAATTCTA CGAAATATTC 2160 AGATAATTTT TCATTTCATT ATTTTCTTTAAGAAAGTTTT ATGATATAAT GTCTTCAATT 2220 AACCAATTTC ATTTAGCAAT TGCCAAAAAATGAAAATAAA GTTTAGGGGT GACTTTTATG 2280 AAGAAAAGTA AATGGTTGGC AGCTGTAAGTGTTGCGATCT TGTCAGTATC CGCTTTGGCA 2340 GCTTGTGGTA ATAAAAATGC TTCAGGTGGCTCAGAAGCTA CAAAAACCTA CAAGTACGTT 2400 TTTGTTAACG ATCCAAAATC ATTGGATTATATTTTGACTA ATGGCGGTGG AACGACTGAT 2460 GTGATAACAC AAATGGTTGA TGGTCTTTTGGAAAACGATG AGTATGGTAA TTTAGTACCA 2520 TCACTTGCTA AAGATTGGAA GGTTTCAAAAGACGGTCTGA CTTATACTTA TACTCTTCGC 2580 GATGGTGTCT CTTGGTATAC GGCTGATGGTGAAGAATATG CCCCAGTAAC AGCAGAAGAT 2640 TTTGTGACTG GTTTGAAGCA CGCGGTTGACGATAAATCAG ATGCTCTTTA CGTTGTTGAA 2700 GATTCAATAA AAAACTTAAA GGCTTACCAAAATGGTGAAG TAGATTTTAA AGAAGTTGGT 2760 GTCAAAGCCC TTGACGATAA AACTGTTCAGTATACTTTGA ACAAGCCTGA AAGCTACTGG 2820 AATTCAAAAA CAACTTATAG TGTGCTTTTCCCAGTTAATG CGAAATTTTT GAAGTCAAAA 2880 GGTAAAGATT TTGGTACAAC CGATCCATCATCAATCCTTG TTAATGGTGC TTACTTCTTG 2940 AGCGCCTTCA CCTCAAAATC ATCTATGGAATTCCATAAAA ATGAAAACTA CTGGGATGCT 3000 AAGAATGTTG GGATAGAATC TGTTAAATTGACTTACTCAG ATGGTTCAGA CCCAGGTTCG 3060 TTCTACAAGA ACTTTGACAA GGGTGAGTTCAGCGTTGCAC GACTTTACCC AAATGACCCT 3120 ACCTACAAAT CAGCTAAGAA AAACTATGCTGATAATATTA CTTACGGAAT GTTGACTGGA 3180 GATATCCGTC ATTTAACATG GAATTTGAACCGTACTTCTT TCAAAAACAC TAAGAAAGAC 3240 CCTGCACAAC AAGATGCCGG TAAGAAAGCTCTTAACAACA AGGATTTTCG TCAAGCTATT 3300 CAGTTGCTTT TGACCGAGCG TCATTCCAAGCACAAACTGC AGGTCAAGAT GCCAAAACAA 3360 AAGCCTTACG TAACATGCTT GTGCCACCAACTTTTGTAAC CGTTGGAGAA AGTGATTTTG 3420 GTTCAGAAGT TGAAAAGGAA ATGGCAAAACTTGGTGATGA ATGGAAAGAC GTTAACTTAG 3480 CTGATGCTCA AGATGGTTTC TATAATCCTGAAAAAGCAAA AGTTGAATTT GCAAAAGCCA 3540 AAGAAGCTT 3549 3200 base pairsnucleic acid double linear DNA (genomic) Streptococcus pyogenes ClinicalIsolate SP-7-44 2 AAGCTTCAAA AATGGCTGGT CTAAAAAAAG TTCCAGCTAT CATCAAGAAGATCTCTACAC 60 TCGAGAGTAT GCAACAAGCT ATAGTTGAAA ATTTACAACG TTCTAACCTTAACGCTATCG 120 AAGAAGCTAA AGCCTATCAG TTATTGGTTG AAAAAAAACA CATGACTCACGATGAGATTG 180 CTAAATATAT GGGAAAATCA AGACCTTATA TTAGCAATAC CTTACGTCTGTTACAACTCC 240 CAGCACCTAT CATTAAAGCA ATTGAAGAAG GAAAAATTAG TGCGGGACACGCGCGTGCTC 300 TTTTAACTTT GAGTGATGAT AAGCAACAAC TGTACCTCAC TCATAAAATACAAAATGAAG 360 GCCTAAGTGT TAGGCAAATT GAGCAACTGG TTACTTCTAC TCCAAGTTCGAAGCTATCTA 420 AAAAAACTAA AAATATTTTT GCCACTTCTT TAGAGAAACA ATTGGCTAAATCATTGGGAC 480 TCTCTGTCAA TATGAAGCTG ACAGCAAACC ATAGTGGGTA CCTTCAGATATCTTTTTCCA 540 ATGATGATGA ATTAAACAGA ATTATCAACA AGCTACTTTA GCTTGTTGATATTCTGTTTT 600 TTCTTTTTTA GTTTTCCACA TGAAAAATAG TTGAAAACAA TAGCGGTGTCACATTAAAAT 660 GGCTTTTCCA CAGGTTGTGG AGAACCCAAA TTAACAGTGT TAATTTATTTTCCACAGGTT 720 GTGGAAAAAC TAACTATTAT CCATCGTTCT GTGGAAAACT AGAATAGTTTATGGTAGAAT 780 AGTGCTAGAA TTATCCACAA GAAGGAACCT AGTATGACTG AAAATGAACAAATTTTTTGG 840 AACAGGGTCT TGGAATTAGC TCAGAGTCAA TTAAAACAGG CAACTTATGAATTTTTTGTT 900 CATGATGCCC GTCTATTAAA GGTCGATAAG CATATTGCAA CTATTTACTTAGATCAAATG 960 AAAGAACTCT TTTGGGAAAA AAATCTTAAA GATGTTATTC TTACTGCTGGTTTTGAAGTT 1020 TATAACGCTC AAATTTCTGT TGACTATGTT TTCGAAGAAG ACCTAATGATTGAGCAAAAT 1080 CAGACCAAAA TCAATCAAAA ACCTAAGCAG CAAGCCTTAA ATTCTTTGCCTACTGTTACT 1140 TCAGATTTAA ACTCGAAATA TAGTTTTGAA AACTTTATTC AAGGAGATGAAAATCGTTGG 1200 GCTGTTGCTG CTTCAATAGC AGTAGCTAAT ACTCCTGGAA CTACCTATAATCCTTTGTTT 1260 ATTTGGGGTG GCCCTGGGCT TGGGAAAACC CATTTATTAA ATGCTATTGGTAATTCTGTA 1320 CTATTAGAAA ATCCAAATGC TCGAATTAAA TATATCACAG CTGAAAACTTTATTAATGAG 1380 TTTGTTATCC ATATTCGCCT TGATACCATG GATGAATTGA AAGAAAAATTTCGTAATTTA 1440 GATTTACTCC TTATTGATGA TATCCAATCT TTAGCTAAAA AAACGCTCTCTGGAACACAA 1500 GAAGAGTTCT TTAATACTTT TAATGCACTT CATAATAATA ACAAACAAATTGTCCTAACA 1560 AGTGACCGTA CACCAGATCA TCTCAATGAT TTAGAAGATC GATTAGTTACTCGTTTTAAA 1620 TGGGGATTAA CAGTCAATAT CACACCTCCT GATTTTGAAA CACGAGTGGCTATTTTGACA 1680 AATAAAATTC AAGAATATAA CTTTATTTTT CCTCAAGATA CCATTGAGTATTTGGCTGGT 1740 CAATTTGATT CTAATGTCAG AGATTTAGAA GGTGCCTTAA AAGATATTAGTCTGGTTGCT 1800 AATTTCAAAC AAATTGACAC GATTACTGTT GACATTGCTG CCGAAGCTATTCGCGCCAGA 1860 AAGCAAGATG GACCTAAAAT GACAGTTATT CCCATCGAAG AAATTCAAGCGCAAGTTGGA 1920 AAATTTTACG GTGTTACCGT CAAAGAAATT AAAGCTACTA AACGAACACAAAATATTGTT 1980 TTAGCAAGAC AAGTAGCTAT GTTTTTAGCA CGTGAAATGA CAGATAACAGTCTTCCTAAA 2040 ATTGGAAAAG AATTTGGTGG CAGAGACCAT TCAACAGTAC TCCATGCCTATAATAAAATC 2100 AAAAACATGA TCAGCCAGGA CGAAAGCCTT AGGATCGAAA TTGAAACCATAAAAAACAAA 2160 ATTAAATAAC ATGTGGAAAA GAATATCTTT TATGAAATAG TTATCCACAAGTTGTGAACA 2220 ACCATTTAGT CTTGGATTCT CTCGTTTATT TAGAGTTATC CACTATATACACAAGACCTA 2280 CTACTACTAC TTATTATTAT ACTTATTAAA TAAAGGAGTT CTCATGATTCAATTTTCAAT 2340 TAATCGCACA TTATTTATTC ATGCTTTAAA TGCAACTAAA CGTGCTATTAGCACTAAAAA 2400 TGCCATTCCT ATTCTTTCAT CAATAAAGAT TGAAGTCACT TCTACAGGAGTAACTTTAAC 2460 AGGGTCTAAC GGTCAAATAT CAATTGAAAA CACTATTCCT GTAAGTAATGAAAATGCTGG 2520 TTTGCTAATT ACCTCTCCAG GAGCTATTTT ATTAGAAGCT AGTTTTTTTATTAATATTAT 2580 TTCAAGTTTG CCAGATATTA GTATAAATGT TAAAGAAATT GAACAACACCAAGTTGTTTT 2640 AACCAGTGGT AAATCAGAGA TTACCTTAAA AGGAAAAGAT GTTGACCAGTATCCTCGTCT 2700 ACAAGAAGTA TCAACAGAAA ATCCTTTGAT TTTAAAAACA AAATTATTGAAGTCTATTAT 2760 TGCTGAAACA GCTTTTGCAG CCAGTTTACA AGAAAGTCGT CCTATTTTAACAGGAGTTCA 2820 TATTGTATTA AGCAATCATA AAGATTTTAA AGCAGTAGCG ACTGACTCTCATCGTATGAG 2880 CCAACGTTTA ATCACTTTGG ACAAATACTT CAGCAGATTT TGATGTGGTTATTCCAAGTA 2940 AATCTTTGAG AGAATTTTCA GCAGTATTTA CAGATGATAT TGAGACCGTTGAGGTATTTT 3000 TCTCACCAAG CCAAATCTTG TTCAGAAGTG AACACATTTC TTTTTATACACGCCTCTTAG 3060 AAGGAAATTA TCCCGATACA GATCGTTTAT TAATGACAGA ATTTGAGACGGAGGTTGTTT 3120 TCAATACCCA ATCCCTTCGC CACGCTATGG AACGTGCCTT CTTGATTTCTAATGCTACTC 3180 AAAATGGTAC TGTTAAGCTT 3200 5014 base pairs nucleic aciddouble linear DNA (genomic) Streptococcus pyogenes Clinical IsolateSP-14-1 3 AAGCTTTTAA GGAGATTTCT TTAGATGCAT TCGTATCTGG TGTTGGTACTGGAGGAACAC 60 TTTCTGGTGT TTCACATGTC TTGAAAAAAG CTAGCCCTGA AACTGTTATCTATGCTGTTG 120 AAGCTGAAGA ATCTGCTGTC TTATCTGGTC AAGAGCCTGG ACCACATAAAATTCAAGGTA 180 TATCAGCTGG ATTTATCCCA AACACGTTAG ATACCAAAGC CTATGACCAAATTATCCGTG 240 TTAAATCGAA AGATGCTTTA GAAACTGCTC GACTAACAGG AGCTAAGGAAGGCTTCCTGG 300 TTGGGATTTC TTCTGGAGCT GCTCTTTACG CCGCTATTGA AGTCGCTAAACAATTAGGAA 360 AAGGCAAACA TGTGTTAACT ATTTTACCAG ATAATGGCGA ACGCTATTTATCGACTGAAC 420 TCTATGATGT GCCAGTAATT AAGACGAAAT AAAAAAGGGT TTGGAACTACTAAGGTTCCA 480 GACTCTTTTT AGTGTTCTTT TTTAAAAACT GCAGGCTTTC TTCAATCCACTGAGGTAACT 540 GCTCTTCAAG TGGCCTAAAG CCAATCTTGT GCCGACTGTT GGAATAACGATGACGATGGA 600 AAAAATGCTG TTTTTCTTCT GCTAAGGTCC GCATAGATAA ACTTGGCTTTTTACTATATT 660 CATCAATATC AATTACTTGT ACTAAAACCT GGTTGCCTAT AGCCAATAATTGATCAATAT 720 CGTCAATAAA TCCCGTTTTT ATTTCTGAAA TATGAATGAG ACCTGTTGTCCCATTTTCAA 780 GGGCAACAAA GGCTCCGTAT GGTTTAATCC CAGTGATGGT GCCATGCAGTTTGTCGCCAA 840 TTTTCATTAG TCAAATACCT CGATTGTTTC AATGATAACG TCTTCTTTAGGTTTATCCTG 900 TGCGCCAGTT TCAACGCCAG CAATCAAATC CAAAACTTGG AATGAAGTTTCGTCCACAAG 960 CTGACCAAAG ACCGTATGAC GACGATCAAG GTGAGGAGTT CCACCAATTGCAGCGTAAGA 1020 AGCTGCAATT GGAGCCGGCC AACCACCACG TTCTAGTTCT TTTTTGGCATAAGGAATCTT 1080 ACTATTTTGA ACAATAAAGA ACTGACTGCC GTTAGTATTT GGTCCCGCATTAGCCATCGA 1140 CAAGGCCCCA CGGAGATTAT AGAGTTCATC CGAAAATTCA TCTTCAAAACTTTCACCATA 1200 GATGGATTGT CCACCCATTC CTGTTCCTGT TGGATCGCCC CCTTGAATCATAAATTCAGG 1260 AATAATACGG TGGAAGATAA TCCCATCATA GTACCCTTCT TTAGCCAAACCTAAGAAATT 1320 GGCTACTGTT TTAGGAGCAT GATCTGGGAA CAAGACCAGG GTCATATCGCCATGGTTTGT 1380 TTTAATGGTT GCTTTTGGTC CTTTATGGTT TGGCAAATCC AATTGTGGAAACTGTAATTC 1440 TTTGTCAATC AATCCTAATT CCTCCAAGGC ATATAAAATG CCATCTTCTTTAACTTTTTT 1500 TGTGATAAAA TCTGCTTTTT CTTGCAGTAA TGGATGTGAT ACTCCCATTGCAATACTGAT 1560 ACCAGCATAG TCAAATAACT CTAGGTCATT GAGTTCATCT CCAAAAACCAAAATGTTTTC 1620 AGGTTTTAAT CCTAAATGGT CAACTACTTT TGAAACACCT AGCGCTTTTGACGTACCTTT 1680 CAAGACAACA TCTGATGAGT TATCGTGCCA TCTGACCAAA CGAAGGTGCTCTGCTAATTC 1740 AGCAGGCAAC TGCAAGCCAT CTCCCTTGTC CTCGAAAGTC CACATCTGGTAAACATCATG 1800 ATACTCATTA TAATCCGGAC AGACCTCTAG TTGAGCGTAG ACATTATCAATAGCATTGCT 1860 AATCATGTCA TTTCGAGCGG ACAACACCGC TTCATGACGA CCCGCCATTCCATAAAAAAT 1920 GCCCATATCA TCCGCCCATT TTTTATAGGC CACAACAACA TCTGCTGGAATCGGAGCTTG 1980 GAAAATAATA GTTTTAGCAT CGTCTTTGAC ATAAGCTCCA TTTAATTTGACACAATAGTC 2040 AGCATGTAAA TCTTGAACTT CTTGTGGAAC ACCGTACCGA GCGCGACCTGAAGCAATACC 2100 AACCAAGATG CCTTTTGCCT TCAAAGCCTT AAATACTCTT TGAATCGACTCAGGCATATA 2160 ACCCGTATCT TTGACCCTCA AGGTATCATC AATATCAAAG AACACCATTTTGATTTTTTT 2220 AGCTTTGTAT TTTAGTTTTG CGTCCATACT TTCCTCCAAT TTGCTATACCCTATATTATA 2280 GCATTAATTA TCGTCTTGGG GGACTAAATG ATGTCGAAAA GCATAGACAACCGCTTGGGT 2340 TCGGTCATCA ACTTCTAACT TGGCTAGAAT ATTGGACACA TGTGTTTTGACGGTTTTTAA 2400 GGAAATAAAG AGTTCATCAG CGATGGTCTG ATTATCATAC CCTTTAGCTAAAAGGTGTAA 2460 AATATCATAC CCACGCGCTG TTAGTTCCTC ATGCAAGTCA GGGTGTTGATCATGCGCCTT 2520 AATTTTTTTG TCAACTTCTG TTTCAATAGC TAACTCTCCC TTTGAAACCTTGCGAATGGC 2580 ATTTAAAATT TCAGCCGCAC TCGATGTTTT TAACATATAA CCCTTCGCTCCTGCATCAAT 2640 GACAGGGTAT ATCTTTTCAT TATCTAGATA GGAAGTTAAC ACAAGTACCTTAGCCTCTTT 2700 CCATTTTTTT AGAACTTCTA AAGTTGCCTC AACACCGCCT AACTCTGGCATCACTAGATC 2760 CATAACCAAA ACATCTGGCT TCAAAGCCAA TGCCAAATCA ACCCCTTCACGTCCATTAGA 2820 GGCCTCACCA ACGACATCAA TATCAGCTTG TAAATTCAAA AAACTCTTGAGTCCCATGCG 2880 GACCATTTCA TGATCATCGA CCAATATCAC TTTTATCTTA CTCATCGTCATCTCCCTTCA 2940 CTATCGGCAG TCTAATATCC ATGGAAACTC CTTTGCCTTT TTGACTAATTAAATGTAGGT 3000 TTCCTGCTAA ATCATTGACA CGGTCTTCAA TATTCTTCAG ACCATAACTCAAATCCCTTA 3060 CCTGATCCAT ATCAAATCCT ACACCATCAT CAATCATCTT CAATTGTAATTCTGTTGAGG 3120 TTTGATTGAG ATAAACTTCA ATTCGACTAG CTTTAGCATG TTTTAACGTGTTGCTAATGA 3180 ATTCTTGGGC AATTCTAAAA AGATTATCTT CCATTGTTTT AGGAAGCTGAGCAATGGTTT 3240 CCTTATAAAT GACTTCAATA TCACTTTTAT CTGTTAATTC CTTAAGAATCATATGAAGGC 3300 CCTCAGATAA AGTCCGATTA GCTAGCTCGG TAGGTCTAAG ATGCAAAAGGAGAATGCGTA 3360 GATCATTTTG AGCATTTTGC AACATTGCTT CAACCGTTGT TAACTGTGTTTGTAATTGTG 3420 TTTTGTCCAG TTGTTCCAAA CTCATTGAAA TTCCTGATAA AATCAATGACGAAGCGAATA 3480 GCTCTTGACT GACTGTGTCA TGTAAATCTC TTGCAATTCG TTTGCGCTCTTGTTTTACAA 3540 CTTCTTGGCT ATCAAGAATA TAAGCACTTT CTTTCTTTTG CATGTTAGCAGTCAGGTGAG 3600 ACATTTTTTT AGAAAGTCGA CTTAAATTAG TATTGATTTC TGATGTCTCATCTAGATAGA 3660 GTCGTCGATT ATTGAGAATA TATTTTAGAT TTTGGTTGAT GTTACGCTTACTGTTATCAT 3720 CCATAATAAT CCACAATAAC AACAATAATA AAGTCACAGA AACAATCAACAATAAAATCG 3780 AAAACCCTAG ACGTTCGACC TGCCATAAAT GATTGCGAAG GTAGTTAAAAGTGATTCCTA 3840 AATTATCCAT GACCACAAAA ACAATAGATA AAATGGTAAT GGTTGAGTAGAGCCAAACAA 3900 GAGCATAGTA ACGTTTTTTC ATCGCCTATC CACCTCAACA TTTCCGGCAATAGTTGTAAC 3960 GATAATTTTG ACTTTTTTAA GGGATTGGTT ATCCGTTTCT TTTAACTTAATAGATTCGTT 4020 GCGCAAATCA TATTGCTGAC ATCTAAAAAA ATCAACACTT CCGTATATGGAACTAACATC 4080 TAAAGTAACA GTGACATCAA TAGGTACCAA TATAGTCGTA TTTCCAAAAATTTTACGTAT 4140 CACAATGATA TTATCCATTC CTGTCACAAT AACATTGGTT AAGTCAACCGTGTCATTTCC 4200 TGAGATTCGA ATGATGTTAA TGTCATCAAA ACAATAATAA TCACTTTCATAATTAGCAGT 4260 ACCAATCCAT TGATGCTTGG TATTGTTCAC TTCAATCTTT TCTTCCTTGAAACGAATCAA 4320 GGCAAAGCGA TTCTTCTTTT TGACTTGTGA AAAATGGTTA ATGAAAATGTAAACTATCCC 4380 CAAAAGAACA GCCATGATAA TGTAGGGATT AAGCATGAAA ATTAAAAAAAGAAACAATAA 4440 ACTGACAGTT AGTAAAAAAT TATTGCGGCT ATCTTGGTTA TAAAAGCGTAATGCTAATAA 4500 GATAAGAACT AGAATTAGGA TAAAACTTGA TAAATCATTA TCCAAGATTGTCATGATACC 4560 CATAGCTAGC AGTATACACT CGATAAGTAA AAAGAATTGA AATTTTTTCATTAGTTTCCC 4620 CTTATTTCTT TGTATTTTAT CAGAATTCCT GGAAAATTGC ATCTTTATATGACGAGTAGT 4680 TAAAAAGAAT AGTTAGTGGC ATGCTAGTAA AACATGAGAC TAACTATTCTTTGTTAAGGT 4740 GTTTGAGCAG TAGTTTCTGA TGGGCTTAAT TCAGTGTTGC TACCTGGTGCAGTACTATCA 4800 TTTGTTGAAG AACTGTTTGA ACTTGACGTT GAACTCGATG AGCTACTAGAAGAGTGTGTT 4860 TCTTCTGGAT AAAGGTAAAG ACTAATCTCT CCTTTATCAG ACAGACTCAAAGACGTTCCA 4920 TAGTAAGGAG ATTGACCACT GACAATAGCT TTAGAACTAG GAGAATGAATTGGCACAAAG 4980 CCCGTTGCTG AGCTAGAGCT TGGCACATAA GCTT 5014 7143 basepairs nucleic acid double linear DNA (genomic) Streptococcus pyogenesClinical Isolate SP-26-36 4 AAGCTTCGCC CTCAAGCCCT TTTTTTCCAA AGGTGGTTTTGTCTCAGTAC CGCCAGTTGT 60 GGCTGCTAAA TTGCTTGGTA AACCAGTCTT TATTCATGAATCAGATCGGT CAATGGGACT 120 AGCAAACAAG ATTGCCTACA AATTTGCAAC TACCATGTATACCACTTTTG AGCAGGAAGA 180 CCAGTTGTCT AAAGTTAAAC ACCTTGGAGC GGTGACAAAGGTTTTCAAAG ATGCCAACCA 240 AATGCCTGAA TCAACTCAGT TAGAGGCGGT GAAAGAGTATTTTAGTAGAG ACCTAAAAAC 300 CCTCTTGTTT ATTGGTGGTT CGGCAGGGGC GCATGTGTTTAATCAGTTTA TTAGTGATCA 360 TCCAGAATTG AAGCAACGTT ATAATATCAT CAATATTACAGGAGACCCTC ACCTTAATGA 420 ATTGAGTTCT CATCTGTATC GAGTAGATTA TGTTACCGATCTCTACCAAC CTTTGATGGC 480 GATGGCTGAC CTTGTAGTGA CAAGAGGGGG CTCTAATACACTTTTTGAGC TACTGGCAAT 540 GGCTAAGCTA CACCTCATCG TTCCTCTTGG TAAAGAAGCTAGCCGTGGCG ATCAGTTAGA 600 AAATGCCACT TATTTTGAGA AGAGGGGCTA CGCTAAACAATTACAGGAAC CTGATTTAAC 660 TTTGCATAAT TTTGATCAGG CAATGGCTGA TTTGTTTGAACATCAGGCTG ATTATGAGGC 720 TACTATGTTG GCAACTAAGG AGATTCAGTC ACCGGACTTCTTTTATGACC TTTTGAGAGC 780 TGATATTAGC TCCGCGATTA AGGAGAAGTA AATGGCAAAAGATAAAGAGA AACAAAGTGA 840 TGACAAGCTC GTTTTGACAG AGTGGCAAAA GCGTAACATTGAATTTTTAA AGAAAAAGAA 900 GCAGCAAGCT GAGGAAGAAA AAAAACTCAA AGAGAAATTATTGAGTGATA AAAAAGCGCA 960 CAGCAAGCTC AAAATGCTTC TGAAGCAGTT GAGCTTAAAACTGATGAGAA AACTGATAGT 1020 CAGGAAATTG AGTCAGAAAC GACGTCAAAA CCTAAAAAACCCAAAAAAGT TAGACAACCC 1080 AAGGAAAAAA GCGCGACACA AATCGCTTTT CAAAAATCCTTGCCTGTTCT TTTGGGGGCG 1140 CTCTTACTTA TGGCGGTGTC TATTTTTATG ATCACTCCTTATAGCAAAAA GAAAGAGTTT 1200 TCTGTAAGAG GAAACCATCA AACGAACCTT GACGAATTAATCAAAGCTAG CAAAGTCAAA 1260 GCATCTGACT ATTGGTTAAC GTTGTTAACT TCGCCTGGTCAGTATGAACG ACCGATTCTT 1320 CGTACTATTC CATGGGTGAA ATCTGTACAT CTCTCTTACCAATTTCCTAA TCACTTTCTA 1380 TTTAACGTTA TTGAATTTGA AATCATCGCT TATGCACAAGTCGAAAACGG TTTTCAGCCT 1440 ATTTTGGAGA ATGGAAAACG TGTGGACAAG GTCAGGGCATCAGAACTACC GAAATCTTTC 1500 TTGATTCTTA ATTTAAAAGA TGAGAAAGCG ATCCAACAGTTAGTTAAGCA ATTAACGACA 1560 TTACCTAAAA AATTAGTCAA GAATATCAAG TCAGTGTCTCTTGCAAATTC CAAAACGACA 1620 GCGGATTTAC TACTTATTGA AATGTATGAC GGTAATGTAGTTAGAGTACC GCAGTCACAA 1680 CTCACATTGA AACTTCCCTA TTATCAAAAA TTGAAAAAAAACCCTTGAAA ATGATAGTAT 1740 AGTGGATATG GAAGTTGGAA TTTACACTAC AACACAGGAGGATTGAAAAT CAACCTGAAG 1800 TTCCTCTTAC GCCAGAACAA AACGCAGCTG ATAAAGAAGGAGATAAGCCT GGTGAGCATC 1860 AGGAACAGAC AGACAATGAT TCAGAAACGC CAGCAAATCAGAGTAGTCCT CAGCAAGCAC 1920 CACCATCCCC AGAAACGGTC CTCGAACAGG CCCATGGCTAGCTAATATCT AAGTTGAAAA 1980 AGCAATGAAA ACGTTAGAAA TTCAACGATT CTAACCCATAATGAATTGCC TAAAAAAAAT 2040 TAAGTTTATA TAACAAAAAA CGTAAAATGA TAACATTTTACGTTTTTTTA TGGTATAATA 2100 TTTTCTGAAT GATTCTGTTT TTTAGCAGTT TTTAGAATAGCAAAAGTTTG GAAAGTAAGT 2160 GAGGTCAAGT GAATGGCTAG AAATGGCTTT TTTACTGGTTTGGACATTGG AACAAGCTCG 2220 ATAAAAGTTT TAGTAGCAGA ATTTATTTCT GGTGAGATGAACGTCATTGG TGTTAGTAAT 2280 GTTCCAAGTA CCGGCGTAAA GATGGCATAA TAATCGATATAGAGGCAGCT GCGACTGCCA 2340 TCAAAACTGC GGTAGAACAA GCAGAAGAAA AAGCAGGGATGACAATTGAA AAGGTTAATG 2400 TTGGGCTACC GGCAAACCTT CTTCAAATTG AACCAACACAAGGAATGATT CCTGTCCCAA 2460 GTGAGTCTAA AGAGATAAAA GATGAGGATG TTGATAGCGTTGTTAAATCG GCTTTAACAA 2520 AAAGTATCAC ACCAGAACGA GAGGTTATCT CTTTAGTTCCAGAAGAGTTC ATTGTGGATG 2580 GCTTTCAGGG CATTCGAGAT CCACGTGGTA TGATGGGGATTAGATTAGAG ATGCGCGGGC 2640 TTATTTATAC TGGACCAAGC ACAATTTTAC ATAATCTGCGTAAAACGGTA GAAAGAGCAG 2700 GCATTAAAGT TGAAAACATC ATTATTTCTC CGTTAGCTATGGCTAAAACC ATTTTAAACG 2760 AAGGTGAGCG CGAGTTTGGA GCTACTGTAA TTGATATGGGAGGTGGACAG ACAACTGTCG 2820 CTTCTATGCG AGCACAAGAA TTGCAGTATA CCAATATATATGCTGAAGGC GGCGAATACA 2880 TTACTAAAGA TATATCAAAA GTATTAAAAA CGTCTTTGGCTATTGCAGAA GCACTTAAGT 2940 TTAATTTTGG TCAAGCGGAG ATATCAGAAG CTAGTATAACTGAAACAGTA AAAGTTGATG 3000 TGGTAGGTAG TGAAGAGCCT GTTGAGGTAA CTGAACGTTATTTTATCTGA AATTATTTCC 3060 AGCGCGTATT CGTCATATTT TAGATCGTGT GAAGCAAGATTTGGAAAGAG GTCGTTTACT 3120 AGACTTACCA GGAGGCATTG TTTTGATTGG TGGCGGTGCAATCATGCCTG GAGTGGTAGA 3180 AATTGCACAA GAAATCTTTG GAGTAACTGT AAAGCTCCATGTTCCAAATC AAGTCGGTAT 3240 TAGAAATCCA ATGTTTTCAA ACGTTATCAG TTTGGTAGAATATGTTGGTA TGATGTCTGA 3300 AGTAGACGTT TTAGCACAAA CTGCAGTTTC AGGAGAAGAACTTTTGCGAC GCAAGCCTAT 3360 CTATTTCAGT GGTCAAGAAT CTTATTTACC AGATTATGATGATTCAAGAA GACCAGAATC 3420 GACCATTGGC TATGAACAAC AAGCGTCACA AACAGCATATGATTCACAAG TTCCGAGTGA 3480 TCCTAAACAA AAAATTTCAG AACGTGTTCG TGGCATATTTGGGAGTATGT TTGATTAAAA 3540 GTAATAAAGT GAGGAGATAA AATGGCGTTT TCATTTGATACTGCATCAAT TCAAGGTGCA 3600 ATTATAAAAG TAATTGGAGT CGGCGGAGGT GGCGGAAATGCCATTAATCG TATGATTGAT 3660 GAAGGTGTTG CTGGTGTCGA GTTCATCGCA GCAAATACAGACATTCAGGC ATTAAGCTCA 3720 TCAAAAGCTG AAACGGTTAT TCAACTAGGC CCTAAATTAACTCGTGGACT TGGTGCTGGA 3780 GGACAACCTG AAGTAGGACG TAAAGCTGCT GAAGAAAGCGAAGAAATTTT AACAGAAGCT 3840 CTTACAGGAG CGGATATGGT ATTTATTACT GCCGGTATGGGTGGTGGCTC TGGGACAGGG 3900 GCTGCACCGG TTATTGCTCG TATCGCTAAG AGTTTGGGAGCCTTGACAGT AGCTGTTGTT 3960 ACTCGCCCGT TTGGTTTTGA AGGTAACAAA CGTGGTAATTTTGCTATTGA AGGTATCGAA 4020 GAACTCCGTG AACAAGTTGA TACTTTGTTA ATTATTTCAAATAATAACCT TCTTGAGATT 4080 GTTGATAAAA AGACACCTTT ATTAGAAGCA CTTAGTGAAGCTGATAATGT TTTACGTCAG 4140 GGAGTTCAAG GGATAACCGA CTTAATTACT AGTCCTGGCCTTATCAATCT CGATTTTGCC 4200 GACGTGAAAA CAGTTATGGC AAATAAAGGG AATGCCTTAATGGGGATTGG GATTGGTTCT 4260 GGAGAAGAGC GCATTGTTGA GGCGGCGCGT AAGGCAATCTATTCACCCCT ATTAGAAACG 4320 ACTATTGATG GTGCACAAGA CGTTATTGTG AACGTTACAGGAGGTCTCGA CATGACACTC 4380 ACAGAAGCTG AAGAAGCCTC TGAAATTGTT GGGCAAGCTGCTGGTCAAGG CGTTAACATT 4440 TGGTTAGGAA CATCTATTGA TGATACTATG AAAGATGACATCCGTGTGAC TGTTGTAGCA 4500 ACTGGAGTGC GCCAAGAAAA AGCCGAACAA GTTTCAGGTTTTCGTCAGCC TAGGACTTTT 4560 ACCCAAACCA ACGCGCAGCA AGTAGCGGGT GCACAATATGCATCAGATCA AGCAAAACAG 4620 TCGGTTCAAC CAGGGTTTGA TCGTCGCTCA AATTTTGATTTTGACATGGG GGAGTCTCGC 4680 GAGATACCAA GTGCACAAAA GGTAATTTCT AATCATAATCAAAATCAAGG TTCTGCTTTT 4740 GGAAATTGGG ATTTGAGACG TGATAATATT TCTCGTCCAACAGAAGGTGA ATTGGATAAC 4800 CATCTTAATA TGTCAACGTT CTCAGCTAAC GATGACAGTGATGATGAATT AGAAACGCCT 4860 CCATTCTTTA AAAACCGTTA ATAATGGATT TACTGACAAATAAAAAGAAA ATTTTTGAGA 4920 CTATCCGCTT ATCTACAGAG GCAGCAAATA GGACTAATGATAGTGTTTCA GTTATTGCTG 4980 TAACAAAATA TGTGGATAGT ACAATTGCAG GTCAGCTTATCGAAGCAGGA ATTGAGCACA 5040 TTGCCGAAAA CCGTGTTGAT AAATTTCTTG AAAAGTATGATGCGTTAAAG TATATGCCAG 5100 TAAAGTGGCA TTTAATCGGT ACCTTACAAC GTCGTAAAGTCAAGGAAGTT ATCAATTATG 5160 TTGATTATTT TCACGCTCTA GATTCTGTGA GATTAGCTTTGGAAATCAAC AAGAGAGCTG 5220 ACCATCCTGT GAAGTGTTTT CTACAAGTTA ATATTTCTAAAGAAGAGAGT AAACATGGTT 5280 TTAACATTTC TGAGATTGAT GAAGCGATTG AAGAAATAGGTAAGATGGAG AAGATACAGT 5340 TAGTTGGTTT AATGACTATG GCACCAGCAA ATGCCAGTAAAGAAAGTATT ATAACTATTT 5400 TTCGACAAGC AAATCAATTA AGAAAAAACT TGCAGTTAAAAAAAAGAAAG AATATGCCTT 5460 TTACAGAATT GAGCATGGGC ATGAGTAACG ATTATCCAATTGCTATTCAA GAAGGCTCAA 5520 CTTTTATTCG GATTGGTAGA GCTTTCTTTC ACTAATGGAGAATAAGATGG CTTTTAAAGA 5580 TACATTTAAC AAGATGATTT CTTATTTTGA CACGGATGAGGTTAACGAAG TTGAAGAAGA 5640 TGTTGCAGCA TCAACTGATA ACGTTATTCC AAGATCACAACAATCAGTCA GAGCAAGTAG 5700 TCATCCAAAA CAAGAACCTA GAAACAATCA CGTACAACAAGATCATCAGG CGAGATCCCA 5760 AGAACAGACA AGGTCACAAA TGCATCCAAA ACATGGTACTTCTGAACGCT ATTATCAGCA 5820 GTCTCAGCCA AAAGAAGGCC ATGAAATGGT TGACAGAAGAAAACGGATGA GCACTTCTGG 5880 TATTGCAAAT CGCCGTGAGC AGTATCAACA ATCAACTTGTTCAGATCAGA CAACTATTGC 5940 CTTAAAATAT CCTCGTAAAT ATGAGGATGC TCAAGAAATTGTGGATCTTT TAATAGTTAA 6000 TGAATGCGTT TTGATTGATT TTCAGTTTAT GCTAGATGCTCAGGCTAGAC GGTGTTTAGA 6060 TTTTATTGAT GGTGCTAGTA AAGTGCTCTA TGGTAGCTTACAAAAGGTCG GCTCTTCAAT 6120 GTACTTACTG GCTCCGTCAA ATGTATCCGT CAATATAGAAGAAATGACTA TCCCACATAC 6180 TACACAAGAT ATTGGCTTTG ATTTTGATAT GAAAAGGCGGTAAATAAATG ATATTAATAC 6240 TATCTATTCT TCTTCGTCTG ATCAAAGTTT ACACTTATTTATTGATTTTA CGCATTAATG 6300 TCATGGTTTC CTGGGGCATA TGATTCAAAA ATTGGGCGTTTGATTAGTGG TATCGTTGAA 6360 CCAATTTTAA AACCTTTTAG AGCATTTAAT TTACAATTTGCCGGTCTTGA CTTCACTATT 6420 TTTGTCGTCA TTATTAGTTT GAATTTTTTA GCTCAAGTTTTGGTCCGTGT GTTTATTTAA 6480 TGGTTAGTCA TAGTAAGATT TATCAGCATT TTCACCAAGAAGAATATCCT TTTATTGATA 6540 GAATGTCTGA TATGATTAAT AGAGTTGGAG ATTACTATCTTTTAGAAGTT ACTGAGTTTT 6600 TAAATCCTAG AGAAGTGATG ATTTTAAAAA GTTTGATTGCTTTAACAGAT CTAAAAATGT 6660 TCGTATCAAC AGATTACTAC CCAAGCGAAT ATGGTCGTGTCATTATTGCA CCTGGTTACT 6720 ATGACTTAGA ACAAAGTGAT TTTCAAATAG CTTTAGTAGAGATAAGTTAT CAGGCAAAGT 6780 TTAATCAGTT GACACATAGT CAAATTTTAG GAACTTTAATTAATGAATTA GGAGTAAAGC 6840 GAAATTTATT TGGAGATGTT TTTGTTGAAA TGGGATATGCCCAGCTCATG ATTAAGCGGG 6900 AGTTATTGGA TTATTTTTTA GGAACAATTA CTAAAATAGCTAAAACTAGT GTGAAATTAA 6960 GAGAAGTTAA CTTTGATCAG TTAATTAGGT CTATTGATAACAGCCAGACC CTGGATATTC 7020 TAGTTTCTAG TTTTCGATTA GATGGTGTAG TTGCTACTATCTTAAAAAAA TCTCGAACGC 7080 AAGTTATAGC ATTAATTGAA GCAAATAAGA TTAAGGTAAACTATCGACTC GCTAATAAAG 7140 CTT 7143 6688 base pairs nucleic acid doublelinear DNA (genomic) Streptococcus pyogenes Clinical Isolate SP-26-46 5AAGCTTCATA TTTTGTTTGG TGCGATCGAC ACCAAGCCTA TTGCGGATAT GTTGGTTGCT 60CTTGAGCAAA TAGGTGACTT GCAGGTTACT GGCTTTCATT ACCCTAACGC CTATCCATTG 120GAAAAATACC CAGAACGTTT TGGTAGGGTT GCTGATTTCA AAGATTTCTT GGCCCTGCGT 180AAGCATGCCA AAGCAGATGA CTTTTTCGTG ATTACAGGGT CGCTATATTT TATTTCAGAA 240ATTAGACAGT ATTGGAAAAA ACATATTGAA AAAAACGTTC TTTTAACCCA TTAAAAAAGA 300GAAAATGAAA AGGAAAAGGA AAAAACTAAT GAAAAGGGAA AGACTAATGT CTATTAATAA 360GGAAAAAGCA GAAGCAGCCA TTTATCAGTT TTTAGAGGCT ATTGGTGAAA ATCCAAATCG 420GGAAGGTCTT CTTGACACGC CTAAACGGGT TGCTAAAATG TATGCGGAGA TGTTTTTGGG 480ACTGGGAAAA GATCCTAAAG AGGAGTTTAC GGCTGTCTTT AAAGAACAAC ATGAGGATGT 540GGTGATTGTC AAAGACATTA GTTTTTATTC TATATGTGAA CACCACTTAG TTCCTTTTTA 600TGGCAAGGCT CATATCGCTT ACTTGCCAAG TGATGGTCGA GTAACAGGTT TGAGTAAATT 660AGCGCGAGCA GTTGAAGTAG CTAGTAAACG ACCTCAACTC CAAGAGCGTT TGACCTCTCA 720AATAGCGGAT GCTTTAGTTG AAGCCCTCAA TCCTAAAGGG ACTTTAGTTA TGGTAGAAGC 780AGAGCACATG TGCATGACCA TGCGAGGCAT CAAAAAGCCA GGTAGTAAAA CCATTACCAC 840CACTGCCAGA GGCTTATATA AGGAAAGTCG TGCTGAGAGG CAAGAAGTTA TTTCTCTAAT 900GACAAAAGAT TAGGAGAACT TATGAAAATT GGAAAGTTTG TGATTGAGGG CAATGCGGCT 960ATCATGGGGA TTTTAAATGT GACTCCAGAT TCTTTTTCAG ATGGGGGGTC TTACACTACT 1020GTGCAAAAAG CATTAGATCA CGTTGAGCAA ATGATTGCTG ATGGGGCTAA AATCATCGAC 1080GTTGGTGGAG AATCAACACG TCCAGGTTGC CAATTTGTAA GCGCTACCGA TGAAATTGAC 1140CGGGTGGTTC CTGTGATCAA GGCCATCAAA GAAAACTATG ATATTCTAAT CAGCATTGAT 1200ACCTATAAAA CCGAAACAGC TAGAGCAGCT TTAGAGGCGG GTGCCGATAT TCTCAATGAT 1260GTTTGGGCAG GTTTGTACGA CGGTCAAATG TTTGCCTTAG CAGCCGAGTA CGATGCGCCT 1320ATCATCTTGA TGCATAACCA AGACGAAGAA GTTTATCAAG AGGTAACACA AGACGTTTGT 1380GATTTTCTAG GCAATAGAGC ACAAGCAGCT CTTGATGCTG GCGTGCCAAA AAACAATATT 1440TGGGTTGATC CAGGATTTGG ATTTGCCAAA TCTGTTCAAC AGAATACGGA GTTATTAAAA 1500GGATTGGACC GCGTCTGTCA TTTGGGCTAT CCTGTCTTGT TTGGTATTTC GAGAAAGCGT 1560GTCGTAGATG CCTTGTTAGG CGGAAACACC AAAGCTAAAG AGCGAGACGG AGCGACAGCA 1620GCCTTGTCTG CTTATGCCCT TGGAAAAGGC TGTCAGATTG TACGCGTACA CGATGTCAAG 1680GCTAATCAAG ACATTGTGGC TGTGTTGAGC CAGTTGATGT GAGGACTTAT GGATAAAATC 1740GTATTAGAAG GTTGCCGTTT TTATGGCTAC CATGGAGCCT TTAAAGAAGA ACAGACCCTT 1800GGGCAAATTT TTCTGGTTGA TTTAGAATTG TCAGTCGATT TGCAAGCAGC TTCTTTGTCA 1860GACCAATTAA CAGATACGGT CCATTACGGG ATGGTGTTTG ATAGTGTCCG TCAGTTAGTG 1920GAAGGGGAAA AGTTTATTTT GATTGAACGT TTAGCAGGTG CGATTTGTGA ACAGCTTTTT 1980AACGAATTTC CGCCTATTGA AGCCATCAAA GTGGCCATTA AAAAGGAAAA CCCACCGATT 2040GCAGGCCACT ATAAGGCAGT TGGTATTGAA TTGGAGAGAC AGAGATGACC ATTGTTTATT 2100TAAGTTTAGG CACCAATATG GGGGACCGAG CAGCTTACTT GCAAAAAGCT CTTGAGGCTT 2160TAGCTGACTT ACCTCAAACA CGGTTGCTTG CTCAATCATC CATTTATGAA ACGACTGCTT 2220GGGGCAAGAC AGGCCAGGCT GATTTTCTCA ATATGGCCTG TCAATTAGAT ACACAATTAA 2280CCGCGGCTGA TTTCTTAAAA GAAACACAAG CTATTGAGCA ATCTCTTGGT CGTGTGAGGC 2340ATGAAAAATG GGGATCAAGA ACTATTGACA TTGATATCTT GCTATTTGGA GAAGAGTTTT 2400ATGACACAAA GGAATTGAAA GTGCCACACC CTTATATGAC TGAGCGTGCT TTTGTTTTAA 2460TCCCCTTATT GGAATTGCAG CCAGATTTAA AATTGCCTCC TAATCATAAG TTTTTAAGGG 2520ATTATCTTGC AGCTTTAGAT CAATCAGATA TCACGCTCTT TTCAGCTCAA CAGACAGAGT 2580TCTAGACTCT GTTTTCGGAG TAATGCCTGC TATAAGCCAA TCCATAAAGT TTTGCCAAAT 2640TCATCGTTAT TTTTTCTAAA ATTTGATATA ATAGTATCGG CTTTATGCCG ATTTTTTTAC 2700GCGTATAAGA AGTGATAAAA GAAAGAAGAT AACTATGATA ACTGAACTTC ATGGGATTGA 2760TATTCGAGAG AATGAACCCC TAAAACATTA CACTTACACT AAGGTAGGTG GCCCAGCAGA 2820TTTCTTGGCT TTTCCTAGAA ATCACTACGA GCTATCACGC ATCGTTGCTT ATGCCAACAA 2880AGAAAATATG CCTTGGCTTG TTTTGGGAAA TGCCAGCAAT CTCATTGTGC GAGATGGTGG 2940TATTCGTGGC TTTGTCATCA TGTTTGATAA GCTAAATGCA GTGCACTTAA ATGGTTATAC 3000CTTAGAAGCC GAAGCTGGTG CCAATCTGAT TGAAACAACG AAGATTGCCA AATTCCATAG 3060TTTAACAGGG TTTGAATTTG CATGTGGCAT TCCTGGAAGC ATTGGGGGTG CTGTTTTTAT 3120GAATGCGGGT GCCTATGGTG GGGAAATATC ACATATTTTC TTATCCGCTA AGGTGCTTAC 3180CTCAAGTGGA GAGATCAAAA CCATTTCAGC TAGGGATATG GCTTTTTGGT TACCGTCACT 3240CTGCCATTCA AGAAACAGGT GACATTGTCA TTTCTGCTAA GTTTGCTCTT AAACCGGGTA 3300ATTATGATAC GATCAGCCAA GAAATGAATC GGTTAAATCA CCTTCGCCAA CTAAAACAAC 3360CTTTAGAATT TCCATCTTGT GGATCTGTGT TTAAGCGCCC GCCAGGACAC TTTGCAGGTC 3420AATTAATCAT GGAAGCAAAT CTTAAAGGGC ATCGGATTGG TGGTGTGGAA GTTTCCGAAA 3480AACACGCTGG TTTTATGATT AATGTGGTAG ATGGCACAGC TAAAGATTAT GAAGATTTGA 3540TTGCTTATGT CATTGAGACA GTTGAAAACC ATTCTGGTGT CAGGCTTGAA CCAGAAGTTC 3600GGATTATTGG GGAAAACCTG TAACCATTTA TTGATAATTA AAGAAAGTAC CGTGGAGGAT 3660TTATGACAAT TGACTAAGCC AATTATCACA TTTAACAATG TTTAAAAAAC ATTTGAGGAC 3720AGTGGAACAC AGGTTCTAAA GAACATTAAC TTTGACCTTG AAGAAGGAAA ATTTTACACC 3780CTGCTTGGAG CTTCTGGCTC TGGAAAATCA ACTATTTTAA ATATTATGGC GGGCCTACTA 3840GATGCCAGCA GCGGAGACAT TTATTTAGAT GGGGAACGTA TTAATGATTT GCCGATTAAT 3900AAACGTGACA TTCATACCGT TTTCCAAAAT TATGCCCTCT TCCCTCATAT GACTGTTTTT 3960GAGAATGTTG CCTTTGCTTT GAAGCTGAAG AAAGTGGACA AGAAAGAGAT TGCTAAGCGC 4020GTGAAAGAAA CCTTGAAAAT GGTTCAATTA GAAGGGTATG AAAATCGTTC TATCCAGAAG 4080TTATCTGGTG GTCAACGTCA ACGTGTTGCC ATTGCGCGTG CGATTATCAA TCAACCGCGT 4140GTGGTCTTAC TTGACGAACC ACTCTCAGCC CTTGATTTGA AATTAAGAAC AGAGATGCAA 4200TATGAATTAC GTGAATTGCA ACAACGTCTA GGCATTACCT TTGTTTTTGT TACTCACGAT 4260CAAGAAGAAG CCTTGGCCAT GAGTGATTGG GTTTTTGTCA TGAATGAAGG TGAAATTGTT 4320CAGTCGGGAA CACCAGTGGA TATTTATGAT GAGCCAATTA ATCATTTTGT TGCTAATTTT 4380ATTGGAGAAT CTAATATTAT TAACGGTACC ATGATTGAAG ACTATCTTGT CTCCTTTAAC 4440GGGAAAGAAT TTGAATCTGT GGACGGTGGG ATGCGCCCTA ATGAGCCTGT TGAAGTGGTT 4500ATTCGTCCTG AAGATCTTCA AATTACTTTG CCAGAAGAAG GGAAATTACA AGTTAAGGTT 4560GATACCCAAT TATTCCGCGG GGTTCACTAC GAAATTATTG CCTATGATGA ATTGGGTAAT 4620GAATGGATGA TTCATTCTAC CCGCAAAGCT ATCGAGGGAG AAGTTATCGG ATTAGACTTT 4680ACCCCTGAAG ATCTTCATAT CATGCGTCTT AATGAGACTG AAGAGGAATT TGATGCCCGT 4740ATTGAAGAAT ATGTGGAAAT GGATGAGCCT GAAGATGGAT TGATTAATGC CATTGAGGAG 4800GAGCGTAATG AAGAAAACCT CTAGTCTTTT TTCGATTCCT TACTTCTTAT GGATTCTCTT 4860CTTTGTTGTG GCACCAGTCA CTCTCTTGTT TTACAAGTCC TTTTTTGACA TAGAAGGGCG 4920CGTGACCTTA GCCAATTATG AAACCTTTTT TAGCTCTTGG ACCTATTTGA GAATGAGTGT 4980GAATTCTATT TTATACGCTG GTATTATCAC ACTCGTCACG CTCTTGATTT CATATCCTAC 5040GGCTCTCTTT TTAACGCGCC TAAAGCACAA GCAGTTGTGG CTTATGCTCA TTATTTTGCC 5100AACTTGGGTA AACTTATTGC TAAAAGCCTA TGCCTTTATG GGAATCTTTG GTCAACAAGG 5160AGGAATTAAC AGCTTTTTAA CCTTTATGGG GATTGGCCCG CAGCAAATCC TTTTCACGGA 5220TTTCTCCTTC ATTTTTGTAG CCTCTTACAT TGAGCTCCCT TTTATGATGT TACCGATTTT 5280TAACGCTTTG GATGATATTG ACCATAATGT CATTAATGCC AGTCGCGACC TAGGAGCTAG 5340TGAATTTCAG GCCTTCTCAA AAGTTATTTT TCCCCTTTCT TTAAATGGGG TTAGGGCAGG 5400TGTTCAGTCT GTCTTTATCC CAAGTTTGAG TCTCTTTATG TTAACCCGTT TGATTGGTGG 5460AAACCGCGTG ATTACACTTG GTACAGCCAT TGAACAACAT TTTTTGACCA CCCAAAACTG 5520GGGAATGGGA TCAACCATAG GTGTGGTGTT AATCTTAACC ATGGTTGCTA TTATGTGGCT 5580CACAAAGGAG AAAAGTAAAT GAAAAAATTT GCCAATCTTT ATTTAGCGAG TGTCTTTGTT 5640TTACTCTACA TTCCTATTTT TTATTTGATT TTCTATTCTT TCAACAAAGG TGGGGATATG 5700AATGGTTTTA CAGGATTTAC CCTTGAGCAT TACCAAACCA TGTTTGAGGA TAGTCGTCTC 5760ATGACAATCT TACTGCAAAC CTTTGTTCTT GCTTTTAGTA GCGCTCTACT AGCAACGATT 5820ATTGGGACCT TTGGAGCTAT CTTTATCCAC CATGTTAGAG GTAAGTACCA AAATGCCATG 5880CTATCAGCCA ATAATGTCTT GATGGTATCA CCAGATGTCA TGATTGGGGC TTCCTTTTTA 5940ATTTTTTTTA CATCATTGAA GTTTCAGCTG GGCATGTCTT CAGTTTTATT AAGTCATATT 6000GCTTTTTCGA TTCCTATTGT GGTTTTGATG GTATTGCCGC GCTTGAAAGA GATGAATCAA 6060GACATGGTCA ACGCCGCTTA TGATTTGGGA GCTAATTATT TCCAAATGCT CAAAGAAGTC 6120ATGCTGCCAT ACTTAACACC AGGGATTATT GCAGGTTATT TTATGGCCTT TACCTATTCC 6180TTAGATGATT TTGCAGTGAC TTTCTTTTTG ACTGGAAATG GTTTTACTAC TTTATCTGTT 6240GAGATTTATT CGCGGGCTCG TCAGGGAATT TCCTTGGATA TCAATGCTTT GTCAACCATC 6300GTTTTCTTTT TCTCCATCCT CTTAGTGATC GGTTATTATT ATATGTCACA GGACAAGGAG 6360GAAAAACATG CGTAAACTTT ATTCCTTTCT AGCAGGAGTT TTGGGTGTTA TTGTTATTTT 6420AACAAGCCTT TCTTTCATCT TGCAGAAAAA ATCGGGTTCT GGTAGTCAAT CGGATAAATT 6480AGTTATTTAT AACTGGGGAG ATTACATTGA TCCAGCTTTG CTCAAAAAAT TCACCAAAGA 6540AACGGGCATT GAAGTGCAGT ATGAAACTTT CGATTCTAAT GAAGCCATGT ACACTAAAAT 6600CAAGCAGGGC GGAACCACTT ACGACATTGC TGTTCCTAGT GATTACACCA TTGATAAAAT 6660GATCAAAGAA AACCTACTCA ATAAGCTT 6688 4973 base pairs nucleic acid doublelinear DNA (genomic) Streptococcus pyogenes Clinical Isolate SP-55-3misc_feature 1934 /note= “N = adenine or cytosine or guanine or thymine”misc_feature 3740 /note= “N = adenine or cytosine or guanine or thymine”6 AAGCTTGTTC AGGTAGGCAC GCAAACAGTC TTAGAACAGT TACCAATGGC GTTAATTGAC 60AAGGGAGTTG TTTTCAGTGA TTTTTATACG GCGCTTGAGG AAATCCCAGA AGTAATTGAA 120GCTCATTTTG GTCAGGCATT AGCTTTTGAT GAAGACAAAC TAGCTGCCTA CCACACTGCT 180TATTTTAATA GCGCAGCCGT GCTCTACGTT CCTGATCACT TGGAAATCAC AACTCCTATT 240GAAGCTATTT TCTTACAAGA TAGTGACAGT GACGTTCCTT TTAACAAGCA TGTTCTAGTG 300ATTGCAGGAA AAGAAAGTAA GTTCACCTAT TTAGAGCGTT TTGAATCTAT TGGCAATGCC 360ACTCAAAAGA CCAGCGCTAA TATCAGTGTA GAAGTGATTG CCCAAGCAGG CAGCCAGATT 420AAATTCTCGG CTATCGACCG CTTAGGTCCT TCAGTGACAA CCTATATTAG CCGTCGAGGA 480CGTTTAGAGA AGGATGCCAA CATTGATTGG GCCTTAGCTG TGATGAATGA AGGCAATGTC 540ATTGCTGATT TTGACAGTGA TTTGATTGGT CAGGGCTCAC AAGCTGATTT GAAAGTTGTT 600GCAGCCTCAA GTGGTCGTCA GGTACAAGGT ATTGACACGC GCGTGACCAA CTATGGTCAA 660CGTACGGTCG GTCATATTTT ACAGCATGGT GTGATTTTGG AACGTGGCAC CTTAACGTTT 720AACGGGATTG GTCATATTCT AAAAGGCGCT AAGGGAGCTG ATGCTCAACA AGAAAGCCGT 780GTTTTGATGC TTTCTGACCA AGCAAGAGCC GATGCCAATC CAATCCTCTT AATTGATGAA 840AATGAAGTAA CAGCAGGTCA TGCAGCTTCT ATCGGTCAGG TTGACCCTGA AGATATGTAT 900TACTTGATGA GTCGAGGACT GGATCAAGAA ACAGCAGAAC GATTGGTTAT TAGAGGATTC 960CTAGGAGCAG TTATCGCTGA AATTCCTATT CCATCAGTCC ACCAAGAGAT TATTAAGGTT 1020TTAGATGAGA AATTGCTTAA TCGTTAAGAC CTACTGCCAA AAAGAAAGAG GTTAGTATTG 1080CTAGACGCAA AAGACATCAA ACAAGACTTT CAAATCTTAA ATCAACAAGT CAATGATGAA 1140CCCCTTGTTT ATTTGGATAA TGCCGCCACC ACACAAAAAC CGGCGCTTGT TCTTGAGGCT 1200TTGCAATCCT ATTATCAAGA AGATAATGCT AATGTCCACC GAGGAGTTCA TACCTTGGCT 1260GAACGTGCAA CGCACAAATA TGAGGCCAGT CGCCAGCAGG TTGCTGACTT TATTCATGCT 1320AAATCAAGTA AGGAAGTGCT CTTTACCAGA GGAACAACAA CCAGTTTGAA TTGGGTTGCT 1380CGGTTTGCAG AGCAGGTCTT GACGCCAGAA GATGAGGTGT TGATTTCGAT TATGGAGCAT 1440CATGCCAATA TCATTCCTTT GGCAACAAGC CTGTCAAAAA ACAGGAGCAA GGTTAGTCTA 1500TGTTTATTTA AAAGATGGCC AACTTGACAT GGACGATTTG GCAAACAAAT TGACGACAAA 1560AACACGTTTT GTTAGCCTAG TACATGTCTC CAATGTTCTT GGTTGCATCA ATCCCATTAA 1620AGAAATTGCC AAGCTGGCAC ATGCTAAAGG AGCCTACCTT GTTGTTGACG GTGCCCAGTC 1680GGTTCCACAT TTGGCTATTG ATGTTCAAGA CTTGGATTGT GATTTCTTTG CTTTTTCAGC 1740TCATAAGATG TTGGGGCCAA CAGGTTTGGG TGTTCTTTAC GGCAAAGAAG AGCTTTTGAA 1800TCAAGTGGAG CCTCTTGAAT TTGGCGGAGA AATGATTGAT TTTGTTTACG AACAAGAGGC 1860CACTTGGAAA GAATTGCCCT GGAAGTTTGA AGCAGGAACA CCTCACATAG CTGGTGCTAT 1920TGGGCTAAGC GCANCCATTT CTTACCTTCA GAGACTAGGC ATGGCTGATA TACATGCGCA 1980TGAAGCAGAA CTAATAGCCT ATGTCTTGCC GAAATTAGAA GCTATTGAGG GGCTTACCAT 2040ATATGGACCA AGCCAGCCTA GTGCAAGATC TGGTCTGATT TCTTTTAATC TGGATGATTT 2100GCATCCTCAT GACTTGGCAA CAGCCTTGGA CTATGAAGGT GTTGCAGTAA GAGCAGGGCA 2160CCACTGCGCC CAACCTCTTC TTAGTTATTT AGGTGTACCA GCAACTGTTA GAGCAAGTTT 2220TTATATCTAT AACACCAAGG CAGATTGTGA CCGTCTAGTC GAAGCAATTC TAAAAGCAAA 2280GGAGTTTTTC AATGGCACTC TCTAAACTGA ACCATCTATA CATGGCTGTG GTAGCGGACC 2340ATTCGAAACG TCCACATCAT CATGGGCAAC TAGATGGCGT AGAGGCTGTT CAACTGAATA 2400ATCCGACTTG TGGTGATGTG ATTTCTTTGA CCGTTAAGTT TGACGAAGAT AAAATTGAAG 2460ATATTGCTTT TGCAGGCAAC GGCTGTACCA TTTCCACAGC TTCATCAAGC ATGATGACAG 2520ATGCTGTTAT TGGTAAAAGT AAAGAAGAAG CACTCGCGTT AGCTGATATT TTTTCAGAGA 2580TGGTACAAGG ACAGGAAAAT CCTGCTCAAA AAGAGCTAGG TGAAGCAGAA TTGTTGGCAG 2640GAGTTGCAAA ATTTCCACAG CGTATCAAAT GCTCTACCCT AGCTTGGAAT GCTCTCAAGG 2700AAGCCATTAA ACGAAGTGCC AATGCTCAGC ACCTCACGGA CCAAAATGTA AAGGAAGGGA 2760AAAATGTCTG ATATAAATGA GAAAGTAGAG CCAAAGCCAA TTGACTTAGG GGACTACCAA 2820TTTGGATTTC ACGATGATGT AGAGCCCATT TATTCTACAG GAAAAGGATT GAGTGAGGCA 2880GTGGTTCGCG AACTATCAGC TGCCAAAAAT GAACCTGAGT GGATGTTGGA GTTTCGTTTA 2940AAATCCTTGG AAACCTTTAA TAAAATGCCG ATGCAAACCT GGGGAGCAGA CTTATCAGAT 3000ATTAACTTTG ATGATATCAT TTACTATCAA AAAGCATCTG ATAAGCCAGC TCGTTCTTGG 3060GATGATGTTC CAGAAAAAAT AAAAGAAACC TTTGATCGTA TTGGAATTCC AGAAGCAGAA 3120CGTGCTTATC TTGCTGGGGC ATCAGCTCAG TATGAGTCAG AAGTGGTTTA CCATAACATG 3180AAGGGTGAAT TTGAAAAGCT AGGGATTATC TTTACAGATA CCGATTCCGC CCTCAAAGAA 3240TATCCTGATT TGTTCAAACA ATACTTTGCC AAACTGGTTC CGCCAACAGA CAACAAATTA 3300GCAGCCCTCA AATTCAGCAG TTTGGTCTGG TGGTACCTTT ATTTATGTTC CTAAAGGGGT 3360CAAGGTAGAT ATCCCTTTGC AAACTTATTT CCGCATTAAC AATGAAAATA CTGGTCAATT 3420TGAGCGGACA TTGATTATTG TTGATGAAGG AGCAAGTGTT CATTATGTTG AAGGATGTAC 3480AGCTCCCACT TATTCAAGTA ACAGCTTACA TGCTGCTATC GTTGAAATCT TTGCGCTTGA 3540CGGTGCATAC ATGCGTTATA CCACCATTCA AAACTGGTCA GACAATGTGT ATAATCTAGT 3600AACAAAACGT GCACGCGCCC TTACGGATGC AACAGTGGAA TGGATTGATG GCAATCTAGG 3660AGCTAAAACC ACCATGAAGT ACCCTTCTGT TTACCTTGAT GGGCCAGGTG CGCGTGGCAC 3720CATGCTGTCT ATTGCCTTTN TAACGCAGGC CAACACCAAG ATACAGGGGC TAAAATGATT 3780CACAATGCTC CCCATACATC ATCATCAATT GTGTCAAAAT CAATTGCCAA GTCTGGTGGT 3840AAAGTAGATT ATCGTGGCCA AGTGACCTTT AACAAGCAAT CTAAAAAATC CGTTTCCCAT 3900ATTGAATGTG ATACTATTTT GATGGACGAT ATTTCTAAAT CAGATACGAT CCCATTTAAC 3960GAAATTCATA ATTCACAGGT GGCGTTAGAA CATGAAGCTA AAGTGTCTAA GATTTCTGAA 4020GAACAACTCT ACTATCTCAT GAGCCGTGGC TTATCAGAAA GCGAAGCCAC AGAGATGATT 4080GTCATGGGAT TTGTGGAGCC TTTTACCAAA GAATTGCCAA TGGAATATGC GGTCGAACTC 4140AATCGATTGA TTTCCTATGA GATGGAAGGT TCTGTCGGTT AATTGCATTT TCTCTTATCC 4200ATCTGAAAGA TCTTTGAGAT AGGATTTTAT GAGTTGTAGT ACTAACCCCA AGTGGTTAGT 4260TTTTAGTTGC CTTGAACACG TAAGATAACA TATCAAAAAC CTCTGTGCTT TGACAGAGGT 4320TTTTGATAAT TCATTATTGG CGTCCCATTG CAAAGACAAC GAGGCTTAGT AAAAGGATAG 4380TAATTATAAA GATAGCTAAG CAAATAAGCA AGAAAGTGTG GTTGTGATTC ATAAAATCTT 4440CGACTCTTTC CAAGTACGAT TGCTTTTTAG TGGCTTTGAA GTGCTGCTGT TTAGGTGATG 4500TTTCTTTTTT GGTTTGTGGC ACTAATTTTT CGAGTTTTTG GCGTGCTTTT TGGATAAGGT 4560CTTACTATCT TTAAACCCTT TCTCAGTCAA GGCATTAACG AAAGGATGTC TATAAAACTC 4620TCCGTTTTGA TCTGACCAAT CTCCGACCCC CATGACAATA GTAATGAGTC GAGTTTTGCC 4680TCTTTTGGCA GTTATCATGG CGTTAAAAGC AGCACTGGGA CTAGAACCTG TTTTTAATCC 4740ATCAACTCCT TTCATACCAA ATTGATTGTC TGGGAGAGAG TGGTTATAGG TGTGAAATTC 4800TTCTTCATAT GGCGTTCCTA CCATAGTGTG CACAACAGAT TTATTTGTAA AGGAGATAAT 4860TTCAGGGTAT TTTTTTAAGA AGGCATAGAG TAACTTGGAC AAATCTCGAG CGGTCGTAAT 4920ATTTGAAGCA GATAAATCAT ATTTAGTAGG ATTATAATAA CCTTGAAAAG CTT 4973 24 basepairs nucleic acid single linear other nucleic acid /desc = “SyntheticDNA” unknown 7 CGACGTTGTA AAACGACGGC CAGT 24 17 base pairs nucleic acidsingle linear other nucleic acid /desc = “Synthetic DNA” unknown 8CAGGAAACAG CTATGAC 17

We claim:
 1. A purified nucleic acid useful as a probe for diagnosinginfectious diseases consisting of a nucleotide sequence selected for thegroup consisting of SEQ ID NOS: 1, 2, 3, 4, 5, and 6, and thecomplements of SEQ ID NOS: 1, 2, 3, 4, 5, and
 6. 2. A purified nucleicacid according to claim 3 consisting of the nucleotide sequence setforth in SEQ ID NO: 1, or the complement of SEQ ID NO:
 1. 3. A purifiednucleic acid according to claim 1 consisting of the nucleotide sequenceset forth in SEQ ID NO: 2, or the complement of SEQ ID NO:
 2. 4. Apurified nucleic acid according to claim 1 consisting of the nucleotidesequence set forth in SEQ ID NO: 3, or the complement of SEQ ID NO: 3.5. A purified nucleic acid according to claim 1 consisting of thenucleotide sequence set forth in SEQ ID NO: 4, or the complement of SEQID NO:
 4. 6. A purified nucleic acid according to claim 1 consisting ofthe nucleotide sequence set forth in SEQ ID NO: 5, or the complement ofSEQ ID NO:
 5. 7. A purified nucleic acid according to claim 1 consistingof the nucleotide sequence set forth in SEQ ID NO: 6, or the complementof SEQ ID NO:
 6. 8. A purified polynucleotide consisting of a nucleotidesequence selected from the group consisting of SEQ ID NOS: 1, 2, 3, 4,5, and 6, and the complements of SEQ ID NOS: 1, 2, 3, 4, 5, and
 6. 9. Aprobe for the diagnosis of infectious disease comprising a purifiednucleic acid according to claim 1, said nucleic acid further comprisinga detectable label.
 10. A probe for the diagnosis of infectious diseasecomprising a purified polynucleotide according to claim 8, saidpolynucleotide further comprising a detectable label.
 11. A purifiednucleic acid useful as a probe for diagnosing infectious diseasesconsisting of a nucleotide sequence selected from the group consistingof SEQ ID NOS: 1, 2, 3, 4, 5, and 6, and the complements of SEQ ID NOS:1, 2, 3, 4, 5, and 6, wherein said nucleic acid hybridizes to genomicDNA of Streptococcus pyogenes, but fails to hybridize to genomic DNA ofStreptococcus agalactiae and Streptococcus pneumoniae, under thefollowing hybridization and washing conditions: hybridization overnightat 42° C. in a hybridization solution comprising 45% formamide and5×SSC; and washing twice for 20 minutes at 55° C., in a washing solutioncomprising 0.1×SSC and 0.1% SDS.
 12. A purified nucleic acid accordingto claim 11 consisting of the nucleotide sequence set forth in SEQ IDNO: 1, or the complement of SEQ ID NO:
 1. 13. A purified nucleic acidaccording to claim 11 consisting of the nucleotide sequence set forth inSEQ ID NO: 2, or the complement of SEQ ID NO:
 2. 14. A purified nucleicacid according to claim 11 consisting of the nucleotide sequence setforth in SEQ ID NO: 3, or the complement of SEQ ID NO:
 3. 15. A purifiednucleic acid according to claim 11 consisting of the nucleotide sequenceset forth in SEQ ID NO: 4, or the complement of SEQ ID NO:
 4. 16. Apurified nucleic acid according to claim 11 consisting of the nucleotidesequence set forth in SEQ ID NO: 5 or the complement of SEQ ID NO: 5.17. A purified nucleic acid according to claim 11 consisting of thenucleotide sequence set forth in SEQ ID NO: 6, or the complement of SEQID NO:
 6. 18. A purified polynucleotide useful as a probe for diagnosinginfectious diseases consisting of a nucleotide sequence selected fromthe group consisting of SEQ ID NOS: 1, 2, 3, 4, 5, and 6, and thecomplements of SEQ ID NOS: 1, 2, 3, 4, 5, and 6, wherein saidpolynucleotide hybridizes to genomic DNA of Streptococcus pyogenes, butfails to hybridize to genomic DNA of Streptococcus agalactiae andStreptococcus pneumoniae, under the following hybridization and washingconditions: hybridization overnight at 42° C. in a hybridizationsolution comprising 45% formamide and 5×SSC; and washing twice for 20minutes at 55° C., in a washing solution comprising 0.1×SSC and 0.1%SDS.
 19. A probe for the diagnosis of infectious disease comprising thepurified nucleic acid according to claim 11, said nucleic acid furthercomprising a detectable label.
 20. A probe for the diagnosis ofinfectious disease comprising the purified polynucleotide according toclaim 18, said polynucleotide further comprising a detectable label.